October 28th

There are many biological tools that help animals ensure reproductive success. A new study published in the August 25, 2014 issue of The Journal of Cell Biology provides further detail into how one such mechanism enables male fruit flies to improve their odds by stopping females from mating with other flies. In addition to sperm, semen carries products that foster sperm survival, promote egg fertilization, and serve other functions that optimize a male's chances of passing along his genes. In male fruit flies, for example, reproductive accessory glands (thought to be equivalent to the prostate gland in humans) secrete signaling factors into the seminal fluid that make the recipient females less inclined to remate. But it's unclear how some of these signaling factors are produced and delivered in order to reprogram a female's behavior against her own self-interest. Researchers from the University of Oxford identified tiny, membrane-bound vesicles called exosomes that are secreted into the seminal fluid by the so-called "secondary cells" of male accessory glands. The authors showed that, after mating, the exosomes fuse with sperm and interact with cells along the female reproductive tract. "Exosomes not only carry ligands that will bind to target cells, but they also carry receptors and intracellular signaling molecules inside them," explains senior author Dr. Clive Wilson, "so they potentially have a lot of possibilities in terms of their ability to reprogram cells." When the researchers reduced the number of exosomes produced by secondary cells, the female flies were more inclined to remate. This indicates that the exosomes are responsible for the behavioral changes, by interacting with the targeted female cells to overpower normal signaling pathways.

Scientists have been laboring to detect cancer and a host of other diseases in people using promising new biomarkers contained in vesicles called "exosomes." Indeed, Popular Science magazine named exosome-based cancer diagnostics one of the 20 breakthroughs that will shape the world this year. Exosomes could lead to less invasive, earlier detection of cancer, and sharply boost patients' odds of survival. "Exosomes are minuscule membrane vesicles — or sacs — released from most, if not all, cell types, including cancer cells," said Dr. Yong Zeng, assistant professor of chemistry at the University of Kansas. "First described in the mid-'80s, they were once thought to be 'cell dust,' or trash bags containing unwanted cellular contents. However, in the past decade scientists realized that exosomes play important roles in many biological functions through capsuling and delivering molecular messages in the form of nucleic acids and proteins from the donor cells to affect the functions of nearby or distant cells. In other words, this forms a crucial pathway in which cells talk to others." While the average piece of paper is about 100,000 nanometers thick, exosomes run just 30 to 150 nanometers in size. Because of this, exosomes are hard to separate out and test, typically requiring multiple-step ultracentrifugation — a tedious and inefficient process requires long stretches in the lab, according to scientists. "There aren't many technologies out there that are suitable for efficient isolation and sensitive molecular profiling of exosomes," said Dr. Zeng. "First, current exosome isolation protocols are time-consuming and difficult to standardize. Second, conventional downstream analyses on collected exosomes are slow and require large samples, which is a key setback in clinical development of exosomal biomarkers." Now, Dr.

Over two hundred visionary scientists, pragmatic physicians, and savvy biotech sales reps from the United States and around the world gathered from October 10-13, 2014, to discuss the latest advances in research and technology related to exosomes, a new and extremely hot area of science with possibly huge potential for game-changing applications in clinical medicine. The occasion was the fourth annual meeting of the American Society for Exosomes and Microvesicles (ASEMV). The site was the magnificently beautiful Asilomar Conference Grounds bordering the Pacific Ocean on Northern California’s Monterey Peninsula. This meeting was organized by Stephen Gould, M.D., President of the ASEMV, Professor of Biological Chemistry at The Johns Hopkins University School of Medicine, and an expert on exosome biogenesis; and by Douglas Taylor, Ph.D., Secretary-General of the ASEMV, formerly a professor at the University of Louisville, an exosome pioneer, and now the chief scientific officer (CSO) of a year-old start-up company called Exosome Sciences, Inc., located just outside Princeton, New Jersey, and a majority-owned subsidiary of Aethlon Medical, Inc. There was also notable organizational assistance from Sasha Vlassov, Ph.D., from Life Technologies (Thermo Fisher Scientific, Inc.), from Travis Antes of System Biosciences, Inc. (SBI), and from many of the graduate students in Dr. Gould’s lab.

Like a colony of bacteria or species of animal, cancer cells within a tumor must evolve to survive. A dose of chemotherapy may kill hundreds of thousands of cancer cells, for example, but a single cell with a unique mutation can survive and quickly generate a new batch of drug-resistant cells, making cancer hard to combat. Now, scientists at the Salk Institute have uncovered details about how cancer is able to become drug-resistant over time, a phenomenon that occurs because cancer cells within the same tumor are not identical–the cells have slight genetic variation, or diversity. The new work, published online on October 22, 2014 in PNAS, shows how variations in breast cancer cells’ RNA, the molecule that decodes genes and produces proteins, helps the cancer to evolve more quickly than previously thought. These new findings may potentially point to a “switch” to turn off this diversity–and thereby drug resistance–in cancer cells. “It’s an inherent property of nature that in a community–whether it is people, bacteria, or cells–a small number of members will likely survive different types of unanticipated environmental stress by maintaining diversity among its members,” says the senior author of the new work, Dr. Beverly Emerson, professor of Salk’s Regulatory Biology Laboratory and holder of the Edwin K. Hunter Chair. “Cancer co-opts this diversification strategy to foster drug resistance.” Instead of looking at a single gene or pathway to target with cancer therapies, lead author Fernando Lopez-Diaz, Ph.D., Salk staff scientist, and the team aim to uncover the diversification “switch” by which cancer cells replicate, but vary slightly from one another. Turning off this cellular process would strip cancer’s ability to survive drug treatment. “Cancer isn’t one cell but it’s an ecosystem, a community of cells,” says Dr. Emerson.

October 27th

Human geneticists have discovered that a region of the genome associated with autism contains genetic variation that evolved in the last 183,000 years, after the divergence of humans from ancient hominids, and likely plays an important role in autism and other diseases. The findings were presented on Saturday evening, October 18, at the opening of the American Society of Human Genetics (ASHG) 2014 Annual Meeting in San Diego, California. Researchers at the University of Washington analyzed the genomes of 2,551 humans, 86 great apes, one Neanderthal, and one Denisovan. The scientists closely examined a region of human chromosome 16 known as 16p11.2, where recurrent deletions and duplications that are major contributors to autism, and also associated with schizophrenia and extremes of body mass and head circumference, occur. Approximately 1% of individuals with simplex autism have deletions or duplication at 16p11.2. These events occur via nonallelic homologous recombination between directly oriented segmental duplications approximately 600 kilobase pairs apart, the presenter, Xander Nuttle, B.S., B.S.E., the first author of the report said. The research team found that certain segments of DNA in this region are repeated a variable number of times in different people and may also be associated with disease. To trace the origins of this variation, the researchers collaborated with colleagues at the University of Lausanne in Switzerland and the University of Bari in Italy to sequence and analyze corresponding regions of ape genomes. Mr.

A possible genetic pathway related to hyperemesis gravidarum (HG), a severe form of morning sickness that affects Kate Middleton, wife of Prince William and mother of young Prince George (see photo), and 0.3 to 2% of all pregnancies, has been identified by Marlena Fejzo, Ph.D., an assistant researcher of hematology–oncology at the David Geffen School of Medicine at UCLA and an assistant professor of maternal and fetal medicine at the Keck School of Medicine of USC, and a team of colleagues. HG disease leads to significant weight loss, dehydration, electrolyte imbalance, and ketonuria. Sixty years ago, HG was the cause of death in 10% of pregnancies, and, even today, it accounts for over 225,000 hospital discharges in the U.S. each year and 15% of HG-afflicted women in the U.S. choose therapeutic termination of pregnancy. The disease remains associated with significant maternal morbidity, including Wernicke’s encephalopathy, renal failure, kidney failure, liver function abnormalities, esophageal rupture, and post-traumatic stress. Genetics has long been thought to play a role in HG, but no definitive study had previously been done. Using exome sequencing in five HG pedigrees and over 470 controls, the Fejzo team identified three kidney disease genes [PKD1, polycystic kidney disease 1 (associated with 85% of autosomal dominant polycystic kidney disease in humans)], PKHD1 (polycystic kidney and hepatic disease 1, associated with autosomal recessive polycystic kidney and hepatic disease 1 in humans), and LAMA5 (laminin alpha 5, a hypomorphic mutation in this gene has been shown to cause polycystic kidney disease in mice) that were found to be variant in the HG families, but in none of the controls.

October 25th

The American Society of Human Genetics (ASHG) has named Suzanne B. Cassidy, M.D., Clinical Professor of Pediatrics in the Division of Medical Genetics at the University of California, San Francisco, as the 2014 recipient of the annual Award for Excellence in Human Genetics Education. The ASHG award recognizes an individual for contributions of exceptional quality and importance to human genetics education internationally. Awardees have had long-standing involvement in genetics education, producing diverse contributions of substantive influence on individuals and/or organizations. Dr. Cassidy received her award, which includes a plaque and monetary prize, on Monday, October 20, 2014 during ASHG’s 64th Annual Meeting in San Diego, California. She delivered her award address immediately thereafter. Dr. Cassidy is well-known for her clinical and research leadership in Prader-Willi syndrome, a genetic disorder that causes low muscle tone, life-threatening obesity, and developmental delays. She has also played key roles in the medical genetics education of medical students, residents, and genetics trainees, as well as of patients and their families. She has developed a variety of education materials, including three editions of the textbook Management of Genetic Syndromes and clinical genetics training programs across the country. “Dr. Cassidy has worked tirelessly to improve genetics education and support patients in a variety of roles – as a teacher, mentor, physician, author, and advocate. This award celebrates her contributions to science, medicine, and the patient experience,” said Joseph McInerney, M.A., M.S., Executive Vice President of ASHG. Throughout her career, Dr.

October 25th

Researchers from the University of Missouri and the 99 Lives Cat Genome Sequencing Initiative announced on October 16, 2014, groundbreaking discoveries of novel mutations in the cat genome found to correlate with two human eye diseases, retinitis pigmentosa and Leber’s Congenital Amaurosis. The 99 Lives Cat Genome Sequencing Initiative is a joint project among the University of Missouri, the University of California, Davis, and industrial partners. The Maverix Analytic Platform was used to analyze this data, and Maverix hosts the Initiative’s genome and analysis data in a publicly-accessible “Community of Discovery.” Leber’s Congential Amaurosis (LCA) is a rare inherited eye disease that primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. LCA is one of the most common causes of blindness in children. With onset at birth or early in life; two to three per 100,000 newborns are born with LCA. Persian cats can suffer from autosomal recessive progressive retinal atrophy (PRA), a disease which is similar to LCA. Association studies of Persian cats localized the causal gene for Persian PRA to cat chromosome E1, which is homologous to human chromosome 17. Whole genome sequencing revealed mutations in the gene AIPL1. A variety of mutations in AIPL1 have been identified as causes of various types of LCA in humans. By finding that the putative causative mutation for Persian PRA is in the gene that can cause LCA in humans, researchers may be able to develop models to better understand the disease pathways associated with this rare eye disease and ultimately develop diagnostic and screening tests that will improve treatment. Retinitis pigmentosa is a condition affecting about 1 in 4,000 people in the United States.

The American Society of Human Genetics (ASHG) has named David Valle (photo), M.D., Henry J. Knott Professor and Director at the McKusick-Nathans Institute of Genetic Medicine of the Johns Hopkins University School of Medicine, as the 2014 recipient of the annual Victor A. McKusick Leadership Award. This award, named in honor of the late Victor A. McKusick, M.D., known widely as the “father of medical genetics,” recognizes individuals whose professional achievements have fostered and enriched the development of human genetics as well as its assimilation into the broader context of science, medicine, and health. ASHG presented the McKusick Award, which will include a plaque and $2,500 monetary prize, to Dr. Valle on Monday, October 20, 2014, during ASHG’s 64th Annual Meeting in San Diego, California. In his acceptance address, Dr. Valle noted that he had had the distinct honor of serving under at least two legendary and towering figures during his long and continuing tenure at Hopkins, namely Victor McKusick and Barton Childs. “Over the years, Dr. Valle has had a tremendous impact on human genetics research, leading various studies and consortia on biochemical genetics and genomics in the United States and internationally,” said Joseph D. McInerney, M.A., M.S., and executive vice president of ASHG. “At the same time, he has maintained a prominent role in improving human genetics education and medical genetics training from K-12 science classes through the postgraduate level,” he added. Dr. Valle’s research focuses on the genetic factors underlying human health and disease, including specific genetic diseases and the broader interactions between genes and the proteins they encode that influence health and disease.

Breaking down complex conditions such as Type 2 Diabetes and obesity into the specific metabolic proteins and processes that underlie them offers a new approach to studying the genetics of these diseases and how they are interrelated, according to research presented on Sunday, October 19, at the American Society of Human Genetics (ASHG) 2014 Annual Meeting in San Diego, California. By studying specific proteins that contribute to such conditions – and the genes that encode them – scientists can develop new drugs that directly target the metabolic processes that do not function properly, explained lead author Jennifer E. Below, Ph.D, of The University of Texas Health Science Center at Houston (UT Health) School of Public Health. “In fact, genes that affect the same process at the protein level can end up influencing multiple traits in tandem,” said Dr. Below. Working with colleagues at the Baylor College of Medicine, Harvard Medical School, and the University of Chicago, Dr. Below found that genes that regulate a person’s circadian cycle affect quality of sleep but could also put him or her at risk for diabetes. Similarly, the researchers learned, a group of related proteins involved in immune system functions and interactions between cells also plays a role in heart health. “Findings such as this highlight the importance of capturing the array of effects of genes, rather than treating each analysis as independent. Traits don’t exist in silos; they are richly connected and interacting, and we benefit by acknowledging this in our genetic analyses,” Dr. Below said. The researchers have focused their efforts in Starr County, Texas, a community where trends in obesity and Type 2 Diabetes rates have steadily remained about 30 years ahead of the rest of the country.